Variations in cocaine binding, metabolism, and acquired tolerance are examined in human male volunteers. Bioavailability comparisons are made for different dosage forms and routes of administration (intravenous, oral, buccal, and inhalation). Plasma and urine cocaine and cocaine metabolite profiles are established as they relate to observed effects and plasma binding is assayed. Assessment of cocaine's effect on cognitive impairment includes symptom and mood change assays, cardiovascular measures, and electroencephalographic responses during auditory signal detection and vigilance tasks.